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To study the association between time to antibiotic administration and survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department.Single-center cohort study.The emergency department of an academic tertiary care center from 2005 through 2006.Two hundred sixty-one patients undergoing early goal-directed therapy.None.Effects of different time cutoffs from triage to antibiotic administration, qualification for early goal-directed therapy to antibiotic administration, triage to appropriate antibiotic administration, and qualification for early goal-directed therapy to appropriate antibiotic administration on in-hospital mortality were examined. The mean age of the 261 patients was 59 ± 16 yrs; 41% were female. In-hospital mortality was 31%. Median time from triage to antibiotics was 119 mins (interquartile range, 76–192 mins) and from qualification to antibiotics was 42 mins (interquartile range, 0–93 mins). There was no significant association between time from triage or time from qualification for early goal-directed therapy to antibiotics and mortality when assessed at different hourly cutoffs. When analyzed for time from triage to appropriate antibiotics, there was a significant association at the <1 hr (mortality 19.5 vs. 33.2%; odds ratio, 0.30 [95% confidence interval, 0.11–0.83]; p = .02) time cutoff; similarly, for time from qualification for early goal-directed therapy to appropriate antibiotics, a significant association was seen at the ≤1 hr (mortality 25.0 vs. 38.5%; odds ratio, 0.50 [95% confidence interval, 0.27–0.92]; p = .03) time cutoff.Elapsed times from triage and qualification for early goal-directed therapy to administration of appropriate antimicrobials are primary determinants of mortality in patients with severe sepsis and septic shock treated with early goal-directed therapy.